Pyridine → 3,5-Dichlorobenzyl 4-(2-(2H-tetrazole-5-carboxamido)ethyl)piperidine-1-carboxylate

HRID 1480390Notes

Reaction equation

HRID 1480390 reaction equation
C(Cl)(=O)C(Cl)=O.CN(C=O)C.[C:12]([C:15]1[N-:19][N:18]=[N:17][N:16]=1)(O)=[O:13].[K+].[NH2:21][CH2:22][CH2:23][CH:24]1[CH2:29][CH2:28][N:27]([C:30]([O:32][CH2:33][C:34]2[CH:39]=[C:38]([Cl:40])[CH:37]=[C:36]([Cl:41])[CH:35]=2)=[O:31])[CH2:26][CH2:25]1.N1C=CC=CC=1>CC#N>[N:16]1[NH:17][N:18]=[N:19][C:15]=1[C:12]([NH:21][CH2:22][CH2:23][CH:24]1[CH2:29][CH2:28][N:27]([C:30]([O:32][CH2:33][C:34]2[CH:39]=[C:38]([Cl:40])[CH:37]=[C:36]([Cl:41])[CH:35]=2)=[O:31])[CH2:26][CH2:25]1)=[O:13]

Participants

7

Reactant 5

HCID 1049PyridineHCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 13596208Potassium 5-carboxytetrazol-1-ideHCID 867226263,5-Dichlorobenzyl 4-(2-aminoethyl)piperidine-1-carboxylate

Product 1

HCID 762841523,5-Dichlorobenzyl 4-(2-(2H-tetrazole-5-carboxamido)ethyl)piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Conditions

Temperature
-20 °C

Procedure

Under nitrogen, oxalyl chloride (58 μl, 0.657 mmol) was dissolved in MeCN (0.5 ml) and cooled to −20° C. DMF (25 μl, 0.329 mmol) was added and the reaction mixture was stirred for 15 minutes. Potassium 5-carboxytetrazol-1-ide (50 mg, 0.329 mmol) was added and the reaction mixture was stirred for a further 20 minutes. A suspension of 3,5-dichlorobenzyl 4-(2-aminoethyl)piperidine-1-carboxylate (Example 3, step 1) (109 mg, 0.329 mmol) and pyridine (32 μl, 0.394 mmol) in MeCN (2 ml) was added and after warming to RT, the reaction mixture was heated at reflux for 1 hr then was allowed to cool. The mixture was evaporated under reduced pressure and the crude product was purified by preparative LC-MS. The product fractions were evaporated under reduced pressure and the residue was partitioned between EtOAc and water. The organic layer was separated, dried over MgSO4 (anh), filtered and evaporated under reduced pressure to afford the title product.

Workup

  1. stirringthe reaction mixture was stirred for a further 20 minutes
  2. additionwas added
  3. temperatureafter warming to RT
  4. temperaturethe reaction mixture was heated
  5. temperatureat reflux for 1 hr
  6. temperatureto cool
  7. customThe mixture was evaporated under reduced pressure
  8. customthe crude product was purified by preparative LC-MS
  9. customThe product fractions were evaporated under reduced pressure
  10. customthe residue was partitioned between EtOAc and water
  11. customThe organic layer was separated
  12. dry with materialdried over MgSO4 (anh)
  13. filtrationfiltered
  14. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-3e85055b91864264bae2ba6c24a03094
Source dataset
uspto-grants-2016_08
Patent number
US09409895B2

Reaction notes

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